Agricultural Lung DiseasesSteven R. Kirkhorn1 and Vincent F. Garry2'Occupational Health Resources, Immanuel St. Joseph's-Mayo Health System, University of Minnesota Rural Family Practice Residency,MankatoNAaseca, Minnesota, USA; 2Laboratory of Environmental Medicine and Pathology, University of Minnesota Medical School,Minneapolis, Minnesota, USA

Agriculture is considered one of the most hazardous occupations. Organic dusts and toxic gasesconstitute some of the most common and potentially disabling occupational and environmentalhazards. The changing patterns of agriculture have paradoxically contributed to both improvedworking conditions and increased exposure to respiratory hazards. Animal confinement operationswith increasing animal density, particularly swine confinement, have contributed significantly toincreased intensity and duration of exposure to indoor air toxins. Ongoing research has implicatedbacterial endotoxins, fungal spores, and the inherent toxicity of grain dusts as causes of upper andlower airway inflammation and as immunologic agents in both grain and animal production. Animalconfinement gases, particularly ammonia and hydrogen sulfide, have been implicated as additionalsources of respiratory irritants. It has become evident that a significant percentage of agriculturalworkers have clinical symptoms associated with long-term exposure to organic dusts and animalconfinement gases. Respiratory diseases and syndromes, including hypersensitivity pneumonitis,organic dust toxic syndrome, chronic bronchitis, mucous membrane inflammation syndrome, andasthmalike syndrome, result from ongoing acute and chronic exposures. In this review we focusupon the emerging respiratory health issues in a changing agricultural economic and technologicenvironment. Environmental and occupational hazards and exposures will be emphasized ratherthan clinical diagnosis and treatment. Methods of prevention, from both engineering controlsand personal respiratory perspectives, are also addressed. Key words: agricultural health,agriculture, animal confinement, endotoxin, grain dust, lung diseases, organic dusts, respiratorydiseases. - Environ Health Perspect 1 08(suppl 4):705-712 (2000).http.//ehpnetl.niehs.nih.gov/docs/2000/suppl-4/705-712kirkhorn/abstract.html

Agriculture is a very diverse industry thatincludes multiple occupational and environ-mental exposures and widely varying workpractices. There are specific respiratory haz-ards associated with the various commoditiesand associated work practices (Table 1).Respiratory disease is one of the main chronicconditions among farmers (1) and also affectsthose in agricultural-related industries. Forexample, respiratory symptoms have beenreported in as many as 93% of veterinarianstreating swine (2). Bioaerosols comprisingorganic dusts, microorganisms, and bacterialendotoxins, and chemical toxicants from fer-mentation and bacterial degradation of grainand animal wastes are the major environmen-tal/occupational health hazards commonlyencountered by farmers, their families, andother agricultural workers. Inorganic dusts areprevalent but less clinically significant.Exposure to each of these toxicant classes orto a combination of these toxicants consti-tutes a risk of respiratory injury.

Changes in the size of agricultural opera-tions and incursion of nonfarm families whomake their homes in the rural setting havealso broadened and increased the opportunityfor significant respiratory exposure-relatedhealth effects in the rural community. Large,high-density animal confinement and animalprocessing facilities are notable in this respect.Animal confinement is of particular interestbecause of the marked changes in animal

husbandry leading to longer and more intenseexposures to dusts and gases as indoor airexposures. Moreover, these operations, andproduction farming in general, are relativelyunregulated, as the majority have fewer than10 employees per employer unit and do notcome under the Occupational Safety andHealth Administration (OSHA) jurisdiction(3). All these factors make measurement diffi-cult of the true extent of agricultural-relatedrespiratory injury and morbidity. In additionto the lack of systematic reporting of agricul-tural respiratory disease, the lack of medicalaccess to healthcare providers in rural areasbecause of cultural and financial issues leadsto significant underreporting.

The application of respiratory protectionprinciples to agriculture is an essential com-ponent of the prevention of agricultural res-piratory illnesses. When applying theagricultural safety hierarchy and principlesof occupational health, engineering controlsare emphasized over personal respiratoryprotection in reducing respiratory hazards.The measurement of airborne dusts, gases,and endotoxins through zone sampling andpersonal breathing zones is the primaryindustrial hygiene technique used to deter-mine the specific hazards and the concentra-tions. This is essential to correct unsafelevels of toxic gases or dusts and to deter-mine the appropriate personal respiratoryprotection. Ventilation is a key component

of decreasing respiratory hazards by increasingfresh air circulating or venting of toxic gasesoutside (4,5). Often, engineering controlsare not sufficient, and personal respiratorsare required to provide additional safe-guards. Personal respirators are either atmos-phere-purifying filters, such as two-strapdust/mist/fume masks or chemical cartridgesthat require a tight facial seal, or atmos-phere-supplying respirators such as the self-contained breathing apparatus (SCBA). Theselection of the appropriate respirator for theconditions encountered and the proper fit isessential for adequate personal respiratoryprotection and is required by OSHA (6).However, production agriculture and fieldoperations with less than 11 employees,which includes the majority of those work-ing in agriculture, are excluded from OSHAsafety regulations and appropriate respira-tory protection principles are sporadicallyand intermittently applied.

The agricultural economic and techno-logic environment is rapidly changing.Currently, it is estimated that up to 5 millionpeople work in U.S. agriculture (7). The1997 agricultural census estimates that indi-vidual farms continue to make up 86% ofthe total farms; 50.3% of farms produce lessthan $10,000 income, and 3.6% produceover $500,000 per year. Five to ten percentof the agricultural work force is engaged inanimal confinement work, with approxi-mately 250,000 working in hog confinementfacilities and another 200,000 in poultryconfinement (8). In 1998 the number of hogoperations was 114,380, with facilities with2,000 or more hogs accounting for 6% of theoperations, but 64% of the total number ofhogs (9). Work in the dairy industry, grainproduction, and sugar beet and potato indus-try also involves confined space work wheresignificant exposure to noxious dusts, pesti-cides, and toxicant gases can occur. Each ofthese sources of respiratory exposure, aloneor in combination, can exert acute andchronic toxicant lung injury.

This article is part of the monograph on Environmentaland Occupational Lung Diseases.

Address correspondence to S.R. Kirkhorn,Occupational Health Resources, 501 Holly Lane, Ste.11, Mankato, MN 56001 USA. Telephone: (507) 625-8282. Telephone: (507) 625-8282. Fax: (507) 625-6760.E-mail: kirkhorn.steven@mayo.edu

Received 7 March 2000; accepted 24 May 2000.

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Table 1. Agricultural respiratory hazards and diseases.a

Categories Sources Environments ConditionsOrganic dusts Grain, hay, endotoxin, Animal confinement Asthma, asthmalike syndrome,

silage, cotton, animal operations, barns, silos, ODTS, chronic bronchitis,feed, animal byproducts, harvesting and processing hypersensitivity pneumonitiscotton, microorganisms operations (Farmer's Lung)

Inorganic dusts Silicates Harvesting/tilling Pulmonary fibrosis, chronicbronchitis

Gases Ammonia, hydrogen Animal confinement Asthmalike syndrome,sulfide, nitrous oxides, facilities, silos, fertilizers tracheobronchitis, silo-filler'smethane, CO disease, pulmonary edema

ChemicalsPesticides Paraquat, organo- Applicators, field Pulmonary fibrosis, pulmonary

phosphates, fumigants workers edema, bronchospasmFertilizers Anhydrous ammonia Application in fields, Mucous membrane irritation,

storage containers tracheobronchitisDisinfectants Chlorine, quarternary Dairy barns, hog confine- Respiratory irritant, broncho-

compounds ment spasmOthers

Solvents Diesel fuel, pesticide Storage containers Mucous membrane irritationsolutions

Welding fumes Nitrous oxides, ozone, Welding operations Bronchitis, metal-fume fever,metals emphysema

Zoonotic Microorganisms Animal husbandry, Anthrax, 0 fever, psittacosisinfections veterinary services

&Adapted from Schenker (68) with additional input from the American Thoracic Society (71, Von Essen and Donham 169, Zjeda andDosman 170, and Donham et al. (71).

DustsInorganilcA tractor tilling a field trailed by large plumesof dust is a common sight throughout therural landscape, but that is not the onlymethod of exposure to inorganic dusts.Diatomaceous earth containing respirable sil-ica is not an uncommon source of respiratoryexposure in different agricultural settings andmay be a cause of bronchitis in workers pro-cessing sugar beets and potatoes in enclosedwork spaces. Very high concentrations ofinorganic dusts are generated by field activi-ties such as plowing, tilling, haying, and har-vesting. The bulk of the inorganic dusts aresilicates. These include crystalline silica(quartz) and noncrystalline amorphous silica(diatomite). Newer tractors with enclosedcabs containing air filtration can decrease res-pirable dust exposure from an average of2-20 mg/m3 to 0.1-1 mg/m3. Inorganic dustcan constitute from 15 to 43% of the totaldust exposure in grain handling. Manual treefruit and grape harvesting are associated withinorganic dust levels greater than OSHA per-missible levels (7). Burning of rice stubble,which contains as much as 12% silica byweight, exposes workers to smoke containingaerosolized silica. Silica is known to causepneumoconioses consisting of restrictive lungdisease and characteristic opacities on chestradiography. California rice farmers had ahigher prevalence of abnormal radiographicfindings than the general population (10).Inorganic dusts, however, do not contributeto agricultural respiratory disease to the same

extent as organic dusts. Furthermore, theweathering effects upon respirable quartzdusts generated by agriculture are consideredto be less pathogenic than the freshly frac-tured quartz dust generated by industrialprocesses such as mining, quarrying, andsandblasting. Diatomaceous silicate inorganicdusts are also considered to have relativelynontoxic pulmonary properties (2).

OrganicGrain dust is a complex mixture of compo-nents including vegetable product, insectfragments, animal dander, bird and rodentfeces, pesticides, microorganisms, endotoxins,and pollens. The primary sources of toxic andallergenic contributors in animal confinementfacilities are animal feces, endotoxins, andpollens. These dust particles range in sizefrom < 0.01 to 100 pm, with up to 40% inthe respirable range. Respirable dusts, definedas having a median diameter of 4.0 pm or lessand hazardous when deposited in the gas-exchange unit area, penetrate to the level ofthe terminal bronchioles and alveoli, the gas-exchange area (11). Respirable dusts in swineconfinement range in concentration from 2to 60% and may reach as high as 40% of thetotal dust. Dust levels are highest in the fin-ishing buildings (up to 15 mg/m3) and from3 to 5 mg/m3 in the farrowing and nurserybuildings (2). The median dust level to whichpoultry workers are exposed was 11.53mg/m3 based on personal sampling (12).Grain dusts are generated from production,harvest, transfer, storage, and processing pro-cedures. The highest grain dust levels are

associated with grain cleaning, with a medianlevel of 72.5 mg/m3 (12). Other high dust-generating environments and work practicesinclude silos, chopping straw for bedding,unloading grain silos, shoveling feed, openingbales of hay for feed, and cleaning old animalhousing structures. Under certain conditionsorganic dusts contain biologically active pro-teins that may be allergenic and proinflam-matory. The biologically active compoundscontained in dust, along with coexisting toxi-cant gases, raise concerns regarding possibleadditive or synergistic toxic exposures andrespiratory health (8).

Specific legal standards for acceptable levelsof organic dust emissions do not exist. Thereis very limited monitoring of dust levels inproduction agricultural settings, as manysmaller operations are excluded from routineOSHA inspections. By default, OSHA per-missible exposure levels (PELs) for nuisancedusts, partides not otherwise regulated, of 15mg/m3 for total dust and 5 mg/m3 for res-pirable dust and 10 mg/m3 for grain dusts(oats, wheat, barley) are used in lieu of a uni-versally accepted upper limit for organic dusts(13). The American Government Council ofIndustrial Hygienists (ACGIH) recom-mended threshold limit value (TLV) for nui-sance dusts is 10 mg/mg3 inhalable and 3mg/m3 respirable (11). The NationalInstitute for Occupational Safety and Health(NIOSH) recommended exposure level(REL) for grain dust is 4 mg/mg3. By contrastinvestigators such as Donham and Reynoldshave determined that dose-response adversepulmonary effects occur at lower total organicdust levels above 2.4-2.5 mg/m3 and res-pirable dust levels of 0.23 mg/m3 for swineconfinement operations and 2.4 mg/m3 totaldust and 0.16 mg/m3 respirable dust in poul-try house operations (14-16) (Table 2). Thesignificant levels were determined to be thosethat caused a 5% decrease in the postshiftforced expiratory volume in 1 sec (FEVI). Asa result of these dose-response findings show-ing a decreased FEV, after a work shift, rec-ommendations have been made for thedevelopment of new threshold-limit stan-dards to adequately protect workers in theanimal confinement industry (14-16).AllergensAllergens encountered indude animal dandersin confinement facilities, and allergenic pro-tein components in grain dusts, particularlythose from wheat sorghum and soy. Biologicmechanisms involved in the inflammatoryresponse indude complement activation, neu-trophil chemotactic activity, and increasedperipheral blood neutrophil response (17,18).Pollens, insect fragments, fungal molds, andbacteria are ubiquitous allergens and can occurat high levels in grain or animal confinement

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enclosed space settings. Noxious allergeniceffects from exposures in enclosed space facili-ties can vary from simple upper respiratoryallergies to bronchial hyperreactivity andasthma. Bronchial hyperreactivity is commonamong workers in swine confinement facilities(8). Reports ofwheezing are more common inagricultural workers than reports of physician-diagnosed asthma. These reports may includethe non-IgE-induced asthmalike syndromedescribed later in the respiratory illnesses andsyndromes section. Other type I allergens,which account for immediate reactions,indude pig epithelium, urine, and saliva (19),and animal feed components containing IgE-inducing food proteins. Storage mites of thespecies Acarus siro, Lepidoglyphys destructor,and Gypcyphagus domesticus have been associ-ated with type I allergic reactions (barnallergy) and are found in warm, humid, andmoldy environments (7,20,21)

Endotoxins and InflammaionIntertwined with these allergenic exposure-related effects is the role of bacterial endotoxinsgenerated in these same environments. Theseheat-stable lipopolysaccharides (LPSs) derivedfrom gram-negative bacteria cell walls can pro-duce flulike symptoms in exposed workers(5,14). LPS contains a biologically active lipid(lipid A) presumed to be responsible for theadverse health effects of endotoxins (5,22).Endotoxins are measured by in vitro biologicassay based upon a Limulus amoebocyte assayand recorded as endotoxin units/cubic meter(EU/m3) or nanograms/cubic meter (ng/m3).One EU is roughly equivalent to 0.1 ng/m3and is dependent upon the potency of the vari-ety of endotoxin. The endotoxin activity ofvarious gram-negative bacteria varies signifi-cantly between species. The genera of gram-negative bacteria that produce endotoxin inagricultural settings include Pseudomonas,Bacillus, Cornyebacterium, Pasteurella, Vibrio,and Enterobacter. Endotoxins are found whereorganic dust is produced and raised by animaland human activities. These conditions arefound in animal confinement structures (swineand poultry), livestock farming, grain elevators,cotton industry, potato processing, flax indus-try, and the animal feed industry.

At higher airborne endotoxin concentra-tions (100-200 ng/m3), bronchoconstrictioncan occur in exposed workers. According tothe International Commission on Occu-pational Health, endotoxin concentrations of1,000-2,000 ng/m3 can result in organic dusttoxic syndrome (ODTS) (7). In the experi-mental setting, it appears that interactionbetween bacterial/fungal spores and endotoxincan be synergistic in the evolution of ODTS(22). Whether endotoxin-mediated pulmonaryeffects are the prime factors in ODTS is uncer-tain, as molds and grain dust extract can alsocontribute to inflammatory pulmonary reac-tions. Furthermore, endotoxins are implicatedas etiologic agents in multiple studies notingdeterioration of pulmonary functions or theoccurrence of chronic respiratory conditionswith evidence of a direct dose-response rela-tionship (15,16,23-26). PELs do not existfor endotoxins, but Donham has recom-mended that 100 EU/i3 (1,000 ng/m3) beestablished as the upper limit of endotoxinvalues for chronic exposure in swine confine-ment operations (14) (Table 2).

Endotoxins are thought to be the cause ofthe inflammatory reaction seen in byssinosis,which is specific to cotton dust exposure andgrain fever (7). Other microbial products maybe inflammatory or immunomodulatory.These include (1,3) P-D-glucans, exotoxinsfrom gram-positive and gram-negative bacte-ria, phytotoxins, heat shock proteins, andT-cell-activating superantigens (7). Furtherresearch is needed to determine what rolethese products play in respiratory disease.

MicroorganismsInfectonFarming, animal husbandry, and animalproduction environments can be reservoirs ofhuman exposure to exotic and commoninfectious agents, resulting in zoonoses. Forexample, hog confinement workers can be atrisk for acquiring swine influenza (27).Poultry workers, particularly those workingwith turkeys and ducks, are at risk for psitta-cosis caused by Chlamydia psittacosis.Veterinarians and zoo workers are also at riskfor developing psittacosis. Q fever, resulting

Table 2. Selected current and recommended maximum agricultural and animal confinement exposures.Animal confine-

Hazard OSHA PEL NIOSH REL ACGIH TLV ment researcha

Nuisance total dust 15 mg/m3 NE 10 mg/m3Nuisance hazard respirable dust 5 mg/m3 NE 3 mg/m3Grain dust 10 mg/m3 4 mg/m3 4 mg/m3Organic dust NE NE NE 2.4-2.5 mg/m3Respirable organic NE NE NE 0.16-0.23 mg/m3Endotoxin NE NE NE 640-1000 ng/m3Ammonia 50 ppm 25 ppm 25 ppm 7.5 ppmNE, not established.Data from Donham et al. (14), Reynolds et al. (15), and Donham et al. (161.

in atypical pneumonia, may result fromaerosolization of the rickettsia Coxiella bur-netti from infected sheep, goats, and cattle.Exposures occur in packing plants, dairies,stockyard facilities, and to sheep farmers andranch hands during the birthing process (27).The incidence of Q fever was found to behigher than expected when surveillance ofNorth Dakota sheep producers was under-taken (28). C. burnetti is a hardy and infec-tious organism, and aerosolized bacteria canbe spread over a half mile, causing commu-nity outbreaks. Mycobacterium bovis isendemic in both wild and farm animals andcan result in tuberculosis infection of veteri-narians, farm workers, abattoir workers, andzookeepers (4).

Of great concern is the emergence ofhantavirus pulmonary syndrome (HPS),which is associated with a significant fatalityrate of 32-40%. This is primarily caused bythe Sin Nombre virus, a single-strandedRNA hantavirus of the Bunyaviradae family.Documented cases have been associated withagricultural activities, including grain farmersand cleaning animal sheds. The exposureresults from the aerosolization of rodenturine, saliva, and droppings found in conta-minated dust in barns and storage facilitiesfor farm equipment (29). The rodent vectors,primarily deer mice (Peromyscus maniculatus),cotton rat (Sigmodon hispidus), rice rat(Oruzp, us palustris), and the white-footedmouse (Peromyscus leucopus), are asympto-matic but are found in enclosed buildings.The initial febrile prodromal symptoms arenonspecific and similar to general viral syn-drome but after 3-5 days may rapidly progressto pulmonary edema resulting in respiratoryfailure requiring mechanical ventilation. HPShas been most commonly associated with theFour Corners area of the Southwestern UnitedStates but may occur throughout the conti-nental United States, Canada, Mexico, andCentral and South America.

Toxic GasesN-itrgen OxidesNitrogen oxides (NO.), the cause of silofiller's disease, are formed during the fermen-tation of silage, with levels reaching concen-trations of several hundred to severalthousand parts per million (7). NO, arepoorly soluble and heavier than air and col-lect in pockets and depressions. Corn andother grain grown under drought conditionswith heavy fertilization can produceextremely high levels of NOx (7). NOX gasesare of low solubility, penetrating to the lowerrespiratory tract, and are severe respiratoryirritants. Fermentation occurs within hours offilling a silo and NO. may reach lethal levelswithin 12 hr; dangerous levels can persist for

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2 weeks afterward. Silos should not beentered during this time without proper res-piratory protection and only after runningblowers for at least 30 min. Measurement ofthe NO. prior to entry of the silo is recom-mended, even after ventilation (30). Acute,usually accidental, high-level exposure can be acause of acute hemorrhagic pulmonary edemaand death. Lower level exposure may producetransient pulmonary decompensation, but pul-monary disease can be a long-term sequela as aresult of fibrotic scarring (31).

Animal Confinement GasesAside from the attendant health risks oforganic dusts, high-density animal confine-ment facilities, and in particular swine con-finement operations, generate high levels ofgases as part of the byproducts of animalwaste. These gases include hydrogen sulfide(H2S), ammonia, carbon dioxide, andmethane. The gases of primary concern areH2S and ammonia. Accidental death due toH2S asphyxiation and or cardiogenic pul-monary edema is rare but can occur in thoseswine or dairy confinement buildings withunder-building manure pits (34. H2S at lowlevels is a respiratory irritant and at higherlevels a chemical asphyxiant. H2S has a lowodor threshold. It is easily detected by the"rotten-egg" smell at 0.13 ppm, a level wellbelow the OSHA PEL of 10 ppm. At increas-ingly higher levels (above 150 ppm), olfactoryparalysis occurs and the odor can no longerbe detected. Pulmonary edema can occur atlevels of 250 ppm and unconsciousness anddeath at 500 ppm. Agitation of manure,which occurs when manure pits are emptied,can release concentrations of H2S as high as1,000 ppm into the breathing zone ofhumans and animals.

Ammonia is a common gas found inanimal and poultry confinement operations.Ammonia is a respiratory and mucous mem-brane irritant. It is very soluble and associ-ated with upper airway irritation, sinusitis,chronic obstructive pulmonary conditions,and mucous membrane inflammation syn-drome. This is discussed in more detail laterin this review. Tolerance can develop withprolonged exposure, leading to fewer irritantsymptoms with greater pulmonary exposure.Prolonged exposure to ammonia at levelsbelow the PEL of 25 ppm has been linked toadverse health effects (15,16). Less consis-tent trends occur with ammonia exposurethan with endotoxin exposure (16). It hasbeen suggested that long-term exposure of> 2 hr/day for 6 years is associated with avariety of conditions, including sinusitis,mucous membrane inflammation syndrome,chronic bronchitis, and asthmalike syn-drome (8). Recommendations have beenmade for exposure levels lower than the

current recommended PELs and TLVs forammonia, as well as dusts, endotoxins, andmicroorganisms (14-16,22) (Table 2).

Unlike H2S, carbon dioxide and methaneare simple asphyxiants and generally are notprimary causes of adverse health effects.Carbon dioxide, produced by animal respi-ration, serves as an indirect indicator of ven-tilation, with acceptable concentrationsbelow 5,000 ppm. Methane at concentra-tions > 5% is also a potential explosive haz-ard (8). Carbon monoxide is not generatedfrom animal wastes but may reach high lev-els as a result of operating gasoline-poweredpressure washers or kerosene heaters inpoorly ventilated buildings. Toxic levelsresulting in carbon monoxide poisoning candevelop within 3-5 min. Even higher levelsconsistent with atmospheres immediatelydangerous to life and health may develop at30 min and result in coma, respiratoryarrest, long-term neurologic complications,and death (33).

Manure pits and lagoons are anaerobicenvironments and considered to be immedi-ately dangerous to life and health inside theconfines of the enclosures. They also containextremely high levels of H2S, methane,ammonia, and carbon dioxide. A person maylose consciousness within seconds and col-lapse into the manure. Those entering to res-cue the fallen individual without SCBA mayalso succumb. Multiple fatalities have occurredand continue to occur every several yearsthroughout the country. The pits and lagoonsshould never be entered without a safety har-ness and properly functioning SCBA. Thosethat survive near-drowning in lagoons candevelop dung lung, a polymicrobial-causedpneumonia (8).

PesticidesAlthough there are well-recognized healtheffects of pesticides, particularly thoseaffecting the central nervous and sympa-thetic/parasympathetic nervous systems,generally speaking and with notable excep-tions, pesticides are not a cause of chronicpulmonary disease. For example, Paraquat,a restricted-use bipyridyl herbicide, is awell-characterized inducer of free radicals inlung tissue and the cause of pulmonaryfibrosis in humans. Intoxication by thecommonly used herbicide Roundup(glyphosphate) may be associated with thedevelopment of chemical pneumonitis.Organophosphates and carbamates, becauseof their effects on cholinesterase, producebronchoconstriction but have no well-docu-mented, long-term pulmonary effects inhumans. Altogether, few pesticides otherthan those cited above are associated withthe development of chronic or acutepulmonary disease.

Respiratory Illnesses andSyndromes

Agricultural respiratory conditions tend tohave an overlapping spectrum (Figure 1).Also, respiratory symptoms caused by agri-cultural exposures are nonspecific and oftenmistaken for common viral or bacterial res-

piratory infections. Unless a careful occupa-

tional history is taken, the proper diagnosismay not be identified. Soluble gases such as

ammonia, normally absorbed into mucous

membranes of the upper airways, adsorbonto dust particles that can penetrate furtherinto the lower respiratory tract than thegases would as a single entity. It is difficultto distinguish the separate adverse effects ofgases and dusts, as they occur together inagricultural environments.

Hypersensitivity PneumonitisSeveral thermophilic actinomyces species,Saccharaopolyspora rectivirgula in particular,and certain Aspergillus fungi species, includ-ing A. fumigatus and A. umbrosus, have beenassociated with farmer's hypersensitivitypneumonitis (FHP), previously referred to as

farmer's lung disease (7). These organismsare found in moldy hay, straw, and feed.FHP is a complex disease that has elementsof an immunologic and cell-mediated allergicresponse that does not fit wholly into any

of the four types of allergic reactions.Continued exposure to antigen in sensitizedindividuals may lead to an antigen-antibodycomplex formation suggesting a type III reac-

tion and a late-phase cell-mediated response

with granuloma formation compatible with a

type IV reaction (34). As an initiating event(acute phase), high-level exposures to moldydusts result in clinical effects symptomati-cally equivalent to ODTS but generally withradiographically demonstrable alveolar lunginfiltrates and oxygen desaturation. More

a1.iTe sp crsator ai as

Chest tightness and aggravation ofand cough on pre-existing asthma I

Organic dustA\txic syndrome // Bronchitis\ 1/ * ~~~~Acute/subchronic* ~~~~~~~Chronic

/ pper aiwy \\/inflammation: \/* Mucous membraine'

irritation syndrome

lleurginc rhinitis ,/ Pulonary edema

Figure 1. The spectrum of respiratory disease in swinernnfine2ment woirkers. Adaptedr frnm kVon Esen anndDonham (69).

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commonly, repeated (subacute) exposures torelatively low levels of antigens in organicdusts lead to the insidious loss of pulmonaryfunction. Pathologically, extensive and local-ized alveolar infiltrates of lymphocytes arenoted in the initial phases of this disease,progressing to the formation of granuloma.However, as the disease progresses, chestX ray shows fibrotic changes in the lungfields. High-resolution chest computedtomography shows evidence of disease,including emphysema, earlier in the course ofdisease (35). In the chronic form of the dis-ease, extensive lung fibrosis occurs (36).Antibodies to thermophilic bacteria andmolds, termed serum precipitins, occur earlyin the course of the disease and are present inup to 90% of individuals with acute symp-toms but tend to wane later in the course ofdisease. Asymptomatic exposed individualsalso have positive serum precipitins, but thisdoes not indicate actual disease. Estimates ofprevalence, based upon positive serum precip-itins, range from 5 to 20% with > 1% havingthe actual disease (20). According to theCanadian Centre for Occupational Healthand Safety, perhaps as many as 2-10% offarm workers in Canada have FHP.

It is to be noted that prevalence of thedisease varies according to climate. FHP ismost common in cool and moist northern di-mates. Symptomatic attacks are more commonin late winter or early spring when stored hayor grains are used to feed livestock. Extremelyhigh levels of bacterial spores can be releasedfrom activities that raise high dust levels.Handling wet moldy hay or feed can releaselevels as high as 100 x 106 spores/g dust com-pared to 5 x 106 spores/g released from dry,properly stored hay and feed (20). If ventila-tion is inadequate, the spore content can be ashigh as 1,600 x 106/m3. Using a beddingchopper to break up straw can increase theconcentration by 50-fold. Interestingly, non-smokers have a higher prevalence of FHPthan smokers. Smoking, however, may resultin a more insidious development of FHPresulting in a chronic form, as acute attackrates were lower and mortality significantlyhigher in smokers with FHP compared tononsmokers with FHP (37). Once sensitiza-tion has occurred, continued exposure to lowlevels of antigen can lead to progressive irre-versible pulmonary disease including emphy-sema. Other agricultural operations areassociated with variants of FHP includingpoultry production, mushroom production,raising of birds, and many other operationsthat process vegetable and animal products.

Guidelines for the diagnosis of FHP havebeen published (38). The recognized criteriato establish the diagnosis include the follow-ing: a) the history and physical findings andpulmonary function tests indicate interstitial

disease; b) the X-ray film is consistent withinterstitial disease; c) there is an exposure to arecognized cause of FHP; and d) there isantibody to the antigen. If these criteria aremet, pulmonary biopsy is not indicated. TheAmerican Thoracic Society ConferenceReport (7) nicely summarized FHP andincluded in the comments: a) FHP leads toprogressive symptoms in at least one-third ofthose affected; b) FHP may be fatal if unrecog-nized; c) recurrences are an important determi-nant of dinical outcome; and d) emphysema isan important outcome of FHP (7). Clearly,early recognition of the sources of exposureand symptoms by farmers and their physiciansis a key to prevention and control of this dis-ease. Decreased exposure to molds and ther-mophilic bacteria can be accomplished bypersonal respiratory protection and work prac-tices designed to decrease dust production andincrease ventilation. These are discussed laterin the prevention section.

Organic Dust Toxic SyndromeTypical ODTS occurs as a result of exposureto mold-laden hays and grains (silo unloader'ssyndrome). ODTS cannot be distinguishedfrom FHP by clinical symptoms. They bothoccur 4-8 hr after exposure and result in self-limited flulike illnesses consisting of chesttightness, shortness of breath, dry cough,fever, chills, myalgias, and fatigue. ODTS isoften misdiagnosed as farmer's lung, which isthe default diagnosis for many respiratory ill-nesses resulting from agricultural exposures,particularly if an adequate exposure history isnot obtained and appropriate testing is notperformed. Medical tests to distinguish thetwo conditions include complete pulmonaryfunction tests, oxygen saturation, and chestradiography. It is probable that ODTS is atoxic reaction rather than an immune reac-tion. Endotoxin is the probable chief cause ofinflammation but endotoxin-free grainextract can also contribute to a pulmonaryinflammatory reaction (39). Unlike FHP,sensitization does not occur, and the condi-tion is not progressive and resolves withinseveral days. The concentration of molds anddust associated with ODTS is approximately10 times greater than that associated withFHP (7). Of interest, this nonallergic acuterespiratory inflammatory disease is highlyprevalent in workers engaged in swine con-finement operations and has been reported ashigh as 34% (8).

On the basis of my personal experience(SK) interviewing attendees at agriculturalhealth fairs and performing clinical evalua-tions, there are many anecdotal reports ofrecurrent attacks with the individuals awareof the precipitating cause. A recent survey ofattendees at an agricultural trade show identi-fied symptoms consistent with ODTS in

36% of those evaluated. Symptoms weresignificantly associated with grain dust expo-sure. Grain sorghum was more strongly associ-ated with respiratory symptoms than othergrains (40). Environmental and work condi-tions associated with ODTS are similar toFHP and include uncapping silos, cleaning outold chicken coops, cleaning up moldy feed,breaking open moldy hay and straw bales, andswine confinement operations. ODTS is morecommon than FHP, particularly in swine con-finement. Preventive measures are similar tothose used to prevent FHP.

Other Respiratory ConditonsAnimal confinement units have been associatedwith newly recognized pulmonary conditionssuch as mucous membrane inflammation syn-drome and asthmalike syndrome. Mucousmembrane inflammation syndrome consistsof nasal, eye, and throat symptoms. Nasallavage has demonstrated immunomodulatoryeffects including increased levels of inter-leukin- 1 a, and interleukin- 1 , and inter-leukin-6 (8). It is the most commonlyreported complex of symptoms in thoseexposed to dusts and gases. The symptoms ofrhinitis have been reported to range from 20to 50% (7).

Farmers and agricultural workers generallyhave a lower prevalence of diagnosed asthmathan the general population, which is thoughtto be due to the healthy worker effect. Thosethat cannot tolerate the exposures and developsymptoms or illnesses tend to leave agricul-tural work. A recent asthma prevalence studyfrom New Zealand reported lower prevalencerates than the general population (41). Astudy of French dairy farmers did not demon-strate an increase in asthma, although otherrespiratory symptoms were increased (42).

Asthmalike syndrome is associated withswine confinement workers and grain elevatoroperators, with acute symptoms reported in asmany as 50% (7). The associated clinicalsymptoms of cough, chest tightness, wheeze,and dyspnea (air hunger) are identical toasthma but lack persistent airway inflamma-tion, increased eosinophils on bronchoalveolarlavage, or significant pulmonary hyperrespon-siveness. With this condition, the symptomsare more pronounced upon return to workafter some time away from exposure, such as aweekend or vacation. This is similar to byssi-nosis in cotton-batting workers or metal-fumefever in welders. Diagnosis can be difficult, asthere is only a small decrement in the FEV,that is temporary and may still be within theaccepted normal values. Often the onlymethod of documenting this is by comparingthe postshift pulmonary function testing tothe preshift pulmonary testing (cross-shifttesting) (23,24). The cross-shift decrease inFEV1 is generally less than 10% (7).

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The prevalence of true occupationalasthma in agriculture is unknown, varies fromcountry to country, and is influenced by thetypes of commodities, work practices, andenvironmental conditions. Occupationalasthma is rare in swine confinement but maybe seen in those exposed to grain, cottondust, and soybean dust.

Other more commonly recognized respira-tory conditions are aggravated by organicdusts and gases associated with agriculturalexposures. Individuals with preexisting asthmaoften do not tolerate working with grain dustor in animal confinement for more than rela-tively short periods of time. Symptoms ofchronic bronchitis, as defined by productivecough for 3 months a year for at least 2 years,are increased in animal and grain productionand grain elevator workers, with a symptomprevalence ranging from 25 to 50%(7,8,43,44). Chronic bronchitis symptoms areassociated with endotoxin exposure (5,45).Swine confinement workers and grain andvegetable farmers have a higher prevalence ofchronic bronchitis symptoms than the generalpopulation (46,44). Smoking in isolation is amajor risk factor in the development ofchronic bronchitis, but several studies haveidentified an additive if not synergistic effectwith agricultural exposures (42,43).Animal Confinement, Odors,and Community HealthNoxious odors emanating from animalconfinement facilities and their manure storagelagoons are an increasingly contentious issue inrural and bordering suburban communities.Gases arising from the decomposition ofmanure, including H2S, methane, and ammo-nia, are one part ofthe many volatile and semi-volatile organic components of the odorantmix (48). Livestock wastes have as many as 168volatile organic compounds. The most impor-tant compounds contributing to odors indudeammonia, diacetyl, volatile fatty acids, phonols,p-cresole, indoles, and skatoles (49. Aside fromthese odorants and potential pulmonary irri-tants, bacteria, fungi, and fungal spores can beinfective or allergenic components of aerosolsarising from the storage lagoons. However, weare not aware of any human health studies orwell-described case studies that specificallyaddress this potentially important respiratoryhealth issue. There are increased environmentalregulations limiting or prohibiting the use ofuncovered manure pits and lagoons that willdecrease the noticeable odors throughout thesurrounding area. The Minnesota PollutionControl Agency currently measures H2S at theproperty boundaries as a proxy for animal con-finement gases when evaluating odor com-plaints. Control methods are instituted if thelevels are repeatedly above the state H2S ambi-ent air standard of30 ppb (50).

Current studies have evaluated sympto-matic health reports of residents living inthe vicinity of swine confinement areas.Depression, fatigue, confusion, and angerwere significantly higher among these persons(51). The other main health complaints consistof eye, nose, and throat irritation, headache,and drowsiness (52). One pilot study indicatedthat neighbors of swine confinement facilitieshad significantly higher rates ofsymptom dus-ters associated with inflammation of the respi-ratory tract (53). A recent population-basedstudy consisting of a survey of health com-plaints in North Carolina showed statisticallysignificant increased upper respiratory symp-toms and cough in community members liv-ing near hog operations, as well as decreasedquality of life. The symptoms mirror thosefound in occupational exposures, but accom-panying environmental monitoring was notperformed (54). The current reporting statusdoes not allow a judgment regarding the sig-nificance of this potential threat to respiratoryhealth. It is uncertain which gas or gasesshould be measured when assessing the air pol-lution effects from large animal confinementoperations. Currently, studies looking into res-piratory conditions resulting from environ-mental exposure to animal confinement gasesare pending in several states. Research needsindude further studies that address the appro-priate environmental monitoring of gases witha prospective case-control assessment of pul-monary and upper airway evaluation accompa-nying the subjective symptom surveys. Effortsto determine dose-response relationships, sim-ilar to those suggested to exist in occupationalexposure studies, should be made (52).

PreventionThe use of personal respiratory devices islimited in agricultural operations because theyare hot and uncomfortable and are not rou-tinely worn. NIOSH-approved two-strap dustand mist respirators are adequate for preven-tion when working in dusty and moldy condi-tions (55). Studies have shown that thetwo-strap masks were effective in preventingfurther attacks of FHP (37). Respiratorsdecreased symptoms in a group of Germanfarmers with occupational asthma but did notcompletely prevent symptoms or the develop-ment of increased airway resistance (56).Severely sensitized individuals with diseasessuch as FHP or exposure to much higher con-centrations of dusts will need more sophisti-cated and expensive respiratory protection witha greater respiratory protection factor to pre-vent further pulmonary deterioration andacute pulmonary injury. A typical example is apowered air-purifying respirator with a faceshield and helmet. Individuals with docu-mented disease and abnormal pulmonaryfunctions should have ongoing medical

surveillance of pulmonary functions andsymptoms to ensure that respiratory protectionis adequate. Chemical cartridges are necessaryfor higher concentrations of organic vaporsand ammonia and should be considered atconcentrations higher than 7.5 ppm. OnlySCBA or air-supplying respirators are adequatefor anaerobic conditions or environmentsimmediately dangerous to life and health dueto high concentrations of noxious gases andvapors. It is essential to recognize that veryimportant barriers to safe work practices areoccupational stressors such as long hours anddire economic conditions, which have beenrecognized as deterrents for the consistent useof appropriate preventive measures, indudingpersonal protective equipment (57).

Engineering controls are preferable tolong-term use of personal respiratory protec-tion. Methods of control include decreasingdust generation by adding mist, adding veg-etable oil to feed, sprinkling oil on the ani-mals, and using wet methods to dean surfaces(58). The use of canola oil sprinkled in aswine room significantly decreased adverserespiratory effects in human subjects and con-comitantly decreased dust, endotoxin levels,H2S, and ammonia (59,60). Fats added tofeeds in the form of canola oil, rapeseed, andmineral oil decreased dust levels by 35-60%in swine confinement buildings (61).Ventilation with proper mixing of airimproves air quality by decreasing dust andgas levels. Mechanical ventilation is recom-mended, as natural ventilation is not reliableor adequate (4). An important method ofdecreasing exposure to toxic levels of gasesand endotoxins is the storage of manure in anenclosed leak-proof structure outdoors.Concentrations of gases should be monitoredperiodically by the use of simple colorimetrictubes or direct-reading electronic monitors.In confined spaces with potentially lethalconcentrations of gases that can rapidlychange, such as silos with NOR, multiplemeasurements with electronic direct-readingmonitors should be obtained prior to fullyopening the door and entering the space (30).Frequent use of disinfectants, wood shavingsfor bedding, and mechanical feeding systemshave been associated with higher prevalenceof respiratory disorders (62,63).

Newer methods of storing silage havedecreased indoor exposure to molds and dusts.Bunkers, plastic-wrapped silage combinedwith outdoor storage, decrease exposure todusts and molds. Capping silage with plasticsheeting decreases decay and mold growth.Harvesting and storing hay, straw, and grainswith moisture content below 30-35% andadding urea as a preservative decreases moldand bacteria growth (42,64). Adding a quartof water to a bale of hay before choppingdecreases dust release by as much as 85% (65).

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An underused resource in agriculturalrespiratory disease prevention is the ruralhealth care provider. It has been recognizedthat health-care providers have had inade-quate training in agricultural health and self-report inadequacies in competency indiagnosing exposure to noxious gases (66,6).Increased knowledge on the part of health-care providers of work practices and environ-mental exposures that have the potential tocause adverse respiratory health effects is animportant component of prevention of agri-cultural respiratory disease (68).

Accessible, accurate, and less-expensivedevices to directly monitor the concentra-tions of dust, gases, and endotoxins in ani-mal confinement operations need to be moreconsistently utilized. Increased routine useof air monitoring of hazardous gases is nec-essary to identify toxic levels. Respiratoryprotection with appropriate protection fac-tors can then be instituted. Dose-responserelationships between organic dust andendotoxin concentrations and adverse pul-monary effects have been demonstrated invarious studies. With this understanding, itis essential to decrease the production ofgases and dusts and provide improved venti-lation technology. The ability to retrofitthese controls upon existing structures at anaffordable cost is very important. If cost isnot considered, a significant number of pro-ducers who cannot afford to build state-of-the-art animal confinement buildings willnot benefit from technologic advances.

SummaryIt is clear that present-day agricultural expo-sures to dusts and gases are associated withacute and chronic respiratory diseases and syn-dromes. Improved engineering controls havedecreased exposures to dusts during field oper-ations through the use of enclosed cabs and airfiltration. Consequences of the evolution inincreasingly larger animal confinement opera-tions include the increased extent and dura-tion of exposure to biologically activerespiratory inflammatory compounds.Improved respiratory hazard controls will beessential to decrease the health risks to farmersand other agricultural workers. For the pre-sent, increased and more universal use of per-sonal respiratory protection duringhigh-exposure procedures is necessary todecrease respiratory exposures to inhaled dustsand gases. Currently, smaller production agri-culture operations with 10 or fewer employeesor individual owner/principle operators gener-ally do not undergo medical surveillance forrespirator use or the detection of pulmonarydeterioration. Further occupational safeguardswill be essential to protect the agriculturalworkers exposed to these potent respiratorytoxins. These efforts will include improved

medical surveillance and the establishment ofTLVs and PELs that adequately protect thehealth of those working in agriculture.

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